The contribution of the non-homologous region of Prs1 to the maintenance of cell wall integrity and cell viability

The gene products of the five-membered PRS gene family in Saccharomyces
cerevisiae have been shown to exist as three minimal functional entities, Prs1/
Prs3, Prs2/Prs5, and Prs4/Prs5, each capable of supporting cell viability. The
Prs1/Prs3 heterodimer can be regarded as the most important because its loss
causes temperature sensitivity. It has been shown that the GFP signal generated
by an integrated GFP-Prs1 construct is lost in the absence of Prs3. In addition
to interacting with Prs3, Prs1 also interacts with Slt2, the MAPK of the cell
wall integrity (CWI) pathway. Lack of the nonhomologous region (NHR1-1)
located centrally in Prs1 abolished the temperature-induced increase in Rlm1
expression. Furthermore, in vitro point mutations generated in PRS1 corresponding
to missense mutations associated with human neuropathies or in the
divalent cation and/or 5-phosphoribosyl-1(a)-pyrophosphate binding sites also
display increased Rlm1 expression at 30 °C and 37 °C and most give rise to
caffeine sensitivity. Human PRPS1 cDNA cannot rescue the synthetic lethality
of a prs1D prs5D strain because it lacks sequences corresponding to NHR1-1 of
yeast Prs1. The correlation between caffeine sensitivity and increased basal
expression of Rlm1 in the altered versions of PRS1 can be extended to their
inability to rescue the synthetic lethality of a prs1D prs5D strain implying that
impaired CWI may contribute to the observed loss of viability.